The two aims of the proposal are: I) to study tumor development in nude mice and characterize the mechanisms of the thymus-independent "resistance" to tumor development ("resistance" in the sense that they generally behave like immunologically normal controls in most parameters of tumor development) and II) to determine if the "natural cytotoxic cells" (NC) found in normal and nude mice, capable of destroying solid tumor targets in vitro, may act as a possible in vivo surveillance mechanism. In brief, our present studies are designed to test the possibility of "alternate pathways" (i.e. non-thymus dependent) of immunological surveillance. The studies for Aim I will be directed towards the characterization of the possible mechanisms operating in the nude mouse, to explain their "normal" tumor incidence. The studies for Aim II will include the characterization of NC cells, the definition of the requirements for target cell susceptibility or resistance, and a comparison between NC cells and other effector mechanisms such as natural killers (NK), antibody-dependent cell-mediated cytotoxicity (ADCC) and macrophage-mediated anti-tumor effects, and the possible in vivo significance of NC cells.